FDA Advisory Committee Votes on Investigational Medicine Metreleptin

Advisory Committee recommends metreleptin for the treatment of pediatric and adult patients with generalized lipodystrophy; does not recommend for the treatment of partial lipodystrophy for the indication currently proposed

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WILMINGTON, Del. & PRINCETON, N.J.

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BMY

NYSE:

AZN

WILMINGTON, Del. & PRINCETON, N.J.--(BUSINESS WIRE)--AstraZeneca
(NYSE:AZN) and Bristol-Myers
Squibb Company (NYSE:BMY) today announced the U.S. Food and Drug
Administration’s (FDA) Endocrinologic and Metabolic Drugs Advisory
Committee (EMDAC) recommends the investigational medicine metreleptin
for the treatment of pediatric and adult patients with generalized
lipodystrophy (LD). Specifically, EMDAC determined by a vote of 11 to 1
that there is substantial evidence that the benefits of metreleptin
exceed the risks for the treatment of pediatric and adult patients with
generalized lipodystrophy.

EMDAC did not recommend metreleptin in patients with partial LD for the
indication currently proposed, by a vote of 2 to 10. AstraZeneca and
Bristol-Myers Squibb remain committed to pursuing metreleptin for
treatment in patients with metabolic disorders associated with partial
LD. The Companies acknowledge the committee’s feedback and will continue
to work with the FDA to identify the appropriate patients with partial
LD who may benefit from metreleptin.

The FDA is not bound by the EMDAC’s recommendation but will take it into
consideration when reviewing the Biologics License Application (BLA) for
metreleptin.

LD is a group of rare syndromes often associated with severe metabolic
abnormalities and significant morbidity and mortality. Metreleptin is
being reviewed by the FDA as a treatment of pediatric and adult patients
with generalized lipodystrophy (LD) or metabolic disorders associated
with partial LD, including hypertriglyceridemia and/or diabetes mellitus
inadequately controlled on a current therapy, and/or evidence of hepatic
steatosis.

The Prescription Drug User Fee Act (PDUFA) goal date for metreleptin is
February 24, 2014. There are no therapies approved by the FDA to treat
patients with rare forms of LD (not including HIV-associated LD).

The EMDAC based its recommendations on a review of data from the
metreleptin clinical development program for LD that supported the BLA
submission, including pivotal efficacy and safety data from two
open-label, investigator-sponsored National Institutes of Health (NIH)
studies, as well as important supplemental efficacy and safety data on
investigational metreleptin from an additional open-label expanded
access study, FHA101.

About the NIH Metreleptin Studies

The first clinical study of investigational metreleptin was initiated in
2000 by investigators at the National Institute of Diabetes and
Digestive and Kidney Diseases (NIDDK), part of NIH. The open-label,
investigator-sponsored pilot study was designed to evaluate the safety
and efficacy of investigational metreleptin administration in patients
with rare forms of generalized or partial LD and did not include
patients with HIV-associated LD. Based on the efficacy data in the pilot
study, a long-term, open-label clinical trial was initiated to determine
the safety and efficacy of investigational metreleptin for improving
metabolic abnormalities in patients with LD, and is currently ongoing.

About Metreleptin

Metreleptin, an investigational recombinant analog of the human hormone
leptin, has received orphan designation from the U.S. Food and Drug
Administration (FDA) and the European Medicines Agency (EMA).
Metreleptin is being evaluated for the treatment of pediatric and adult
patients with generalized LD or metabolic disorders associated with
partial LD, including hypertriglyceridemia and/or diabetes mellitus
inadequately controlled on a current therapy, and/or evidence of hepatic
steatosis.

About Lipodystrophy

LD is a group of rare syndromes often associated with severe metabolic
abnormalities and significant morbidity and mortality. It is estimated
to affect only a few thousand people worldwide. LD is heterogeneous in
presentation and often occurs at an early age – during childhood or in
early adulthood. There are several reasons for developing LD. In some
patients, it is genetic, and in others it may be acquired for different
reasons, including cases in which the immune system may attack and
destroy existing fat tissue. Sometimes, clearly defined reasons for the
development of the condition are unknown.

Whether genetic or acquired in origin, all forms of LD share a common
pathophysiology: loss of fat tissue, especially fat under the skin. This
loss of fat tissue, which causes a deficit in the hormone leptin, can
vary from complete loss, or “generalized,” to loss of fat in only some
parts of the body, or “partial.” Without enough fat tissue or leptin,
the body’s system for regulating energy use and storage falls out of
balance. The resulting serious imbalance causes lipid to accumulate
where it should not be found—such as in the liver and muscle—which may
lead to severe metabolic abnormalities, primarily hypertriglyceridemia,
severe insulin resistance with resultant hyperglycemia and type 2
diabetes, and hepatic steatosis (fatty liver disease).

The metabolic abnormalities in patients with LD are often difficult to
control even with high doses of currently available diabetes and
lipid-lowering therapies. These therapies are rendered less effective by
the profound insulin resistance associated with LD. Moreover, these
therapies are not designed to correct the underlying deficiency of
leptin. Patients with LD are left with the burden of these chronic and
uncontrolled metabolic abnormalities, which can be associated with
premature mortality often due to acute pancreatitis, renal failure,
severe cardiac disease, or liver failure. Therefore, there is a
significant unmet medical need for a therapy that improves the metabolic
disorders found in these patients.

About the AstraZeneca / Bristol-Myers Squibb Diabetes Alliance

Dedicated to addressing the global burden of diabetes by advancing
individualized patient care, AstraZeneca and Bristol-Myers Squibb are
working in collaboration to develop and commercialize a versatile
portfolio of innovative treatment options for diabetes and related
metabolic disorders that aim to provide treatment effects beyond glucose
control. Find out more about the Alliance and our commitment to meeting
the needs of health care professionals and people with diabetes at www.astrazeneca.com or www.bms.com.

About AstraZeneca

AstraZeneca is a global, innovation-driven biopharmaceutical business
that focuses on the discovery, development and commercialization of
prescription medicines, primarily for the treatment of cardiovascular,
metabolic, respiratory, inflammation, autoimmune, oncology, infection
and neuroscience diseases. AstraZeneca operates in over 100 countries
and its innovative medicines are used by millions of patients worldwide.
For more information please visit: www.astrazeneca.com.

About Bristol-Myers Squibb

Bristol-Myers Squibb is a global biopharmaceutical company whose mission
is to discover, develop and deliver innovative medicines that help
patients prevail over serious diseases. For more information, please
visit http://www.bms.com or
follow us on Twitter at http://twitter.com/bmsnews.

Bristol-Myers Squibb Forward Looking Statement

This press release contains "forward-looking statements" as that term
is defined in the Private Securities Litigation Reform Act of 1995
regarding product development. Such forward-looking statements are based
on current expectations and involve inherent risks and uncertainties,
including factors that could delay, divert or change any of them, and
could cause actual outcomes and results to differ materially from
current expectations. No forward-looking statement can be guaranteed.
Among other risks, there can be no guarantee that metreleptin will
receive FDA approval, that the timing of any such approval will occur
within the time period described in this release or that, if approved,
it will become a commercially successful product. Forward-looking
statements in this press release should be evaluated together with the
many uncertainties that affect Bristol-Myers Squibb's business,
particularly those identified in the cautionary factors discussion in
Bristol-Myers Squibb's Annual Report on Form 10-K for the year ended
December 31, 2012, in our Quarterly Reports on Form 10-Q and our Current
Reports on Form 8-K. Bristol-Myers Squibb undertakes no obligation to
publicly update any forward-looking statement, whether as a result of
new information, future events or otherwise.